Friday, June 29, 2012

What's new for 'Trypanosomatids' in PubMed

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results
Items 1 - 8 of 8

1. Electrophoresis. 2012 Jul;33(12):1901-10. doi: 10.1002/elps.201200007.

CE-ESI-MS metabolic fingerprinting of Leishmania resistance to antimony treatment.

Canuto GA, Castilho-Martins EA, Tavares M, López-Gonzálvez A, Rivas L, Barbas C.

Source

Center for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid, Spain; Institute of Chemistry, University of São Paulo (USP), Campus São Paulo, São Paulo, Brazil.

Abstract

Metabolomics has become an invaluable tool to unveil biology of pathogens, with immediate application to chemotherapy. It is currently accepted that there is not one single technique capable of obtaining the whole metabolic fingerprint of a biological system either due to their different physical-chemical properties or concentrations. In this work, we have explored the capability of capillary electrophoresis mass spectrometry with a sheathless interface with electrospray ionization (CE-ESI-TOF-MS) to separate metabolites in order to be used as a complementary technique to LC. As proof of concept, we have compared the metabolome of Leishmania infantum promastigotes BCN 150 (Sb (III) IC(50) = 20.9 μM) and its variation when treated with 120 μM of Sb(III) potassium tartrate for 12 h, as well as with its Sb(III) resistant counterpart obtained by growth of the parasites under increasing Sb(III) in a step-wise manner up to 180 μM. The number of metabolites compared were of 264 for BCN150 Sb(III) treated versus nontreated and of 195 for Sb(III) resistant versus susceptible parasites. After successive data filtering, differences in seven metabolites identified in databases for Leishmania pathways, showed the highest significant differences, corresponding mainly to amino acids or their metabolite surrogates. Most of them were assigned to sulfur containing amino acids and polyamine biosynthetic pathways, of special relevance considering the deterioration of the thiol-dependent redox metabolism in Leishmania by Sb(III). Given the low concentrations typical for most of these metabolites, the assay can be considered a success that should be explored for new biological questions.

© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID: 22740478 [PubMed - in process]
2. J Invest Dermatol. 2012 Jun 28. doi: 10.1038/jid.2012.205. [Epub ahead of print]

Immunity to Sand Fly Salivary Protein LJM11 Modulates Host Response to Vector-Transmitted Leishmania Conferring Ulcer-Free Protection.

Gomes R, Oliveira F, Teixeira C, Meneses C, Gilmore DC, Elnaiem DE, Kamhawi S, Valenzuela JG.

Source

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.

Abstract

Leishmania vaccines that protect against needle challenge fail against the potency of a Leishmania-infected sand fly transmission. Here, we demonstrate that intradermal immunization of mice with 500 ng of the sand fly salivary recombinant protein LJM11 (rLJM11) from Lutzomyia longipalpis, in the absence of adjuvant, induces long-lasting immunity that results in ulcer-free protection against Leishmania major delivered by vector bites. This protection is antibody independent and abrogated by depletion of CD4(+) T cells. Two weeks after challenge, early induction of IFN-γ specifically to rLJM11 correlates to diminished parasite replication in protected animals. At this time point, Leishmania-specific induction of IFN-γ in these mice is low in comparison with its high level in non-protected controls. We hypothesize that early control of parasites in a T-cell helper type 1 environment induced by immunity to LJM11 permits the slow development of Leishmania-specific immunity in the absence of open ulcers. Leishmania-specific immunity observed 5 weeks after infection in rLJM11-immunized mice shows a twofold increase over controls in the percentage of IFN-γ-producing CD4(+) T cells. We propose LJM11 as an immunomodulator that drives an efficient and controlled protective immune response to a sand fly-transmitted Leishmania somewhat mimicking "leishmanization"-induced protective immunity but without its associated lesions.Journal of Investigative Dermatology advance online publication, 28 June 2012; doi:10.1038/jid.2012.205.

PMID: 22739793 [PubMed - as supplied by publisher]
3. Rev Esp Enferm Dig. 2012 Jun;104(6):333.

Visceral leishmaniasis diagnosed by double balloon enteroscopy.

Gómez-Espín R, Fuentes E, López-Espín MI, Bebia P, Esteban P, Chacón S, J L Rodrigo, López-Higueras A, Pérez-Cuadrado E.
PMID: 22738708 [PubMed - as supplied by publisher]
4. Bioorg Med Chem Lett. 2012 Jun 7. [Epub ahead of print]

Discovery of nitroheterocycles active against African trypanosomes. In vitro screening and preliminary SAR studies.

Arán VJ, Kaiser M, Dardonville C.

Source

Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain.

Abstract

A selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite Trypanosoma brucei rhodesiense, causative agent of human African trypanosomiasis (HAT). The unspecific cytotoxicity of the compounds was also evaluated against rat myoblast L6-cells to measure the selectivity of the compounds towards the parasite. This screening revealed some preliminary structure-activity relationships (SAR) among the series, and six hit compounds showing interesting activity (IC(50)⩽10μM) and fair selectivity (SI>17). The 7-nitroquinoxalin-2-one and 5-nitroindazole scaffold derivatives 58 and 35, respectively, are particularly interesting because of their established oral bioavailability in mice. These hits represent interesting starting points for a medicinal project aimed at identifying the SAR behind this class of compounds.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22738640 [PubMed - as supplied by publisher]
5. J Vector Borne Dis. 2012 Mar;49(1):54.

Insect vectors of Leishmania: distribution, physiology and their control.

Sharma U, Singh S.
PMID: 22737744 [PubMed - in process]
6. Parasitology. 2012 Apr;139(4):516-21. Epub 2012 Feb 6.

Trypanosoma cruzi discrete typing units in Chagas disease patients from endemic and non-endemic regions of Argentina.

Cura CI, Lucero RH, Bisio M, Oshiro E, Formichelli LB, Burgos JM, Lejona S, Brusés BL, Hernández DO, Severini GV, Velazquez E, Duffy T, Anchart E, Lattes R, Altcheh J, Freilij H, Diez M, Nagel C, Vigliano C, Favaloro L, Favaloro RR, Merino DE, Sosa-Estani S, Schijman AG.

Source

Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Ingeniería Genética y Biología Molecular, Vuelta de Obligado 2490, 2do piso, 1428, Ciudad de Buenos Aires, Argentina.

Abstract

Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.

PMID: 22309735 [PubMed - indexed for MEDLINE]
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7. Placenta. 2012 Apr;33(4):264-70. Epub 2012 Jan 31.

Differential susceptibility of isolated human trophoblasts to infection by Trypanosoma cruzi.

Díaz-Luján C, Triquell MF, Schijman A, Paglini P, Fretes RE.

Source

Placenta and Chagas Laboratory, Cell Biology, Histology and Embryology Department, Medicine Faculty, Universidad Nacional Córdoba, Enrique Barros y Enfermera Gordillo, CP 5000, Córdoba, Argentina. cintiadiaz@yahoo.com

Abstract

The aim of the work was to analyze the susceptibility of the placental syncytiotrophoblast (STB) and cytotrophoblast (CTB) cells to infection by the causal agent of congenital Chagas' disease, Trypanosoma cruzi, and the possible parasite route for placental invasion. Monolayers of CTB and STB and VERO as control cells were used. The infection of STB was significantly lower that of the CTB and Vero cells (p < 0.05) which coincided with a significantly increased mortality of parasite cells in the culture medium and trypanocidal levels of nitric oxide. We conclude that the syncytiotrophoblast, the first placental barrier, is the main barrier of the chorionic villous that limits the infection by T. cruzi. This work opens the possibility of a new mechanism for placental infection when there are discontinuities in the first placental barrier.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22296856 [PubMed - indexed for MEDLINE]
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8. Parasitology. 2012 Apr;139(4):506-15. Epub 2012 Jan 5.

Study of Trypanosoma cruzi epimastigote cell death by NMR-visible mobile lipid analysis.

Benitez D, Pezaroglo H, Martínez V, Casanova G, Cabrera G, Galanti N, González M, Cerecetto H.

Source

Grupo de Química Medicinal, Laboratorio de Química Orgánica, Universidad de la República, Montevideo, Uruguay.

Abstract

Cell death mechanisms in Trypanosoma cruzi have not been disclosed in detail though different conventional techniques have been used in the classification of parasite-cell death type. Nuclear magnetic resonance (NMR) has successfully been used as a tool to evaluate the onset of apoptosis in a number of higher eukaryote-cell models analysing the ratio of CH(2)/CH(3) integration from the visible mobile lipids (VML). Surprisingly, this versatile non-invasive spectroscopy technique has never been employed with this purpose in T. cruzi. In the present study it is shown that under different parasite death-conditions the ratio CH(2)/CH(3) varied drastically. Thus, T. cruzi epimastigotes in apoptotic conditions increase significantly this ratio while in necrotic as well as in autophagic situations the parasites maintain the VML, CH(2)/CH(3) ratio, in normal values. Additionally, other VML markers commonly used in these studies, such as the change in the region of methyl-choline moiety, -N(+)(CH(3))(3), exhibited different particular patterns according to the type of cell death. Our results suggest that the (1)H NMR-VML technique is an adequate tool to discriminate different T. cruzi death pathways.

PMID: 22216891 [PubMed - indexed for MEDLINE]
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